Differential effects of histamine on Leydig cell and testicular macrophage activities in wall lizards: precise role of H1/H2 receptor subtypes

Abstract

The present study in the wall lizard, Hemidactylus flaviviridis, was aimed to understand the role of histamine (HA) in the regulation of Leydig cell and testicular macrophage activities, for the first time, in ectothermic vertebrates. Although HA did not affect the testosterone production from unstimulated Leydig cells, it had dual concentration-related effects, stimulatory at a low concentration of 10 K10 M while inhibitory at a high concentration of 10 K5 M, on FSH-induced testosterone production. This suggests that HA did not influence the basal Leydig cell steroidogenesis, but modulated the FSH-stimulated testosterone production in a biphasic manner depending upon its concentration. However, HA failed to affect the FSHstimulated Leydig cell proliferation, indicating that HA modulated the testosterone production from Leydig cells without influencing their proliferation in wall lizards. HA, apart from Leydig cells, differentially regulated the testicular macrophage immune responses. It inhibited phagocytosis and superoxide production at high concentration (10 K5 M), while stimulated superoxide production and could not affect phagocytosis at low concentration (10 K10 M). Using selective H1 and H2 antagonists, pyrilamine and famotidine respectively, H1 receptor subtype was seen responsible for mediating the inhibitory effect of HA on Leydig cell steroidogenesis and testicular macrophage immune responses at high concentration, while H2 receptors were involved for the stimulation at low concentration.

Immunocytochemical Tools Reveal a New Research Field Between the Boundaries of Immunology and Reproductive Biology in Teleosts

“…Moreover, in 180 dph juveniles, acidophilic granulocytes and mesenchymal cells and a few germ cells produced Il1 , while in 270 dph males, in which the spermatogenesis process is active, Il1 was only located in acidophilic granulocytes and spermatocytes as occurs in one year old fish (Chaves-Pozo et al, 2008a). Our observations of the gonadal primordial support the hypothesis that Il1 is a testicular germ cell growth factor, as is also the case in mammals, since Il1 is not produced in the developing ovarian area (Khan and Rai, 2007;Parvinen et al, 1991;Pollanen et al, 1989). The appearance of Mcsfr was only observed in the well-developed testicular areas of 240-300 dph males, produced by the same cell types as in the adult testis (Chaves-Pozo et al, 2008a).…”

Histamine inhibits adrenocortical cell proliferation but does not affect steroidogenesis

“…The existence of a functional histaminergic system in the testis of different species has been demonstrated previously by us (Mondillo et al 2005, Pagotto et al 2012 and others (Mayerhofer et al 1989, Pap et al 2002, Albrecht et al 2005, Khan & Rai 2007. Particularly, we have reported that low concentrations of HA (10 K9 M) stimulate LC steroidogenesis and higher concentrations (10 K5 M) inhibit it (Mondillo et al 2005).…”

H4 histamine receptors inhibit steroidogenesis and proliferation in Leydig cells

“…We previously demonstrated that tumor MA-10 cells behave in a similar manner to their normal equivalent in terms of HA-induced regulation of acute steroidogenesis (Mondillo et al 2005(Mondillo et al , 2009), while they respond differently to HA when it comes to cell proliferation (Khan & Rai 2007, Pagotto et al 2012. Thus, to evaluate whether the observed effect of HRH4 agonists on the proliferation of MA-10 cells could be extrapolated to their normal Effect of an HRH3 agonist on basal and hCG-stimulated progesterone production in MA-10 cells and on MA-10 cell proliferation.…”

“…HA-synthesizing mast cells and HA receptors are present in the diverse compartments of the testis in several species, including human: HRH1 and HRH2 have been detected in germ and peritubular cells, as well as in macrophages and Leydig cells (Albrecht et al 2005, Mondillo et al 2005, 2007, Khan & Rai 2007, and HRH1 has also been found in the testicular capsule (Nemetallah et al 1983). Accordingly, numerous studies from our group and others over the past few years have documented the ability of HA to modulate Leydig cell steroidogenesis through HRH1 and HRH2 (Mayerhofer et al 1989, Mondillo et al 2005, 2007, Khan & Rai 2007, and a very recent publication from our group has suggested a role for HA as an autocrine-paracrine regulator of Leydig cell proliferation under testicular pathological conditions (Pagotto et al 2012).…”

“…Accordingly, numerous studies from our group and others over the past few years have documented the ability of HA to modulate Leydig cell steroidogenesis through HRH1 and HRH2 (Mayerhofer et al 1989, Mondillo et al 2005, 2007, Khan & Rai 2007, and a very recent publication from our group has suggested a role for HA as an autocrine-paracrine regulator of Leydig cell proliferation under testicular pathological conditions (Pagotto et al 2012). Considering that germ cells express HDC (Safina et al 2002), and that HA has been implicated in spermatogenesis, penile erection and sexual behavior as well as steroidogenesis (Cara et al 1995, Par et al 2003, Sinha et al 2006), it appears that the amine plays an integral role in the regulation of male reproductive function, which certainly deserves further investigation.…”